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Genetic Welfare Problems of Companion Animals

An information resource for prospective pet owners

Quarter Horse

Belgian Draft Horse

Junctional Epidermolysis Bullosa

Related terms: JEB, equine epitheliogenesis imperfecta, hereditary junctional mechanobullous disease, red foot disease, hairless foal syndrome; epitheliogenesis imperfecta neonatorum

Outline:  Foals with junctional epidermolysis bullosa have a defect in the gene responsible for the attachment of the outer layers of the skin to the underlying tissue. As a result, blisters form in between the layers of the skin, specifically between the layers of the basement membrane underlying the epidermis. These blisters rapidly progress to erosions and deep ulcerative lesions, especially at pressure points or after mild trauma. In the worst cases, it can lead to the loss of the hoof because it affects the layers of the skin above the hoof (the coronary band).


Summary of Information

(for more information click on the links below)

1. Brief description

The epidermis of the skin is the protective outer layer, and is composed of several layers of cells. At the base of the epidermis, there is a layer called the basement membrane and this connects the epidermis above to the dermis layer below it. The basement membrane is composed of two layers, the basal lamina and the underlying layer of connective tissue in the dermis, which connects to the basal lamina by collagen anchoring fibrils and fibrillin microfibrils.

Foals with junctional epidermolysis bullosa have a defect in the gene responsible for the attachment of the outer layers of the skin to the underlying tissue. As a result, only the inner layer of the basement membrane is properly anchored to the underlying dermal collagen and where this pulls away from the outer basement layer blisters form. These blisters, which can be extensive and cover large areas of skin, rapidly progress to erosions and deep ulcerative lesions, especially at pressure points or after mild trauma. In severe cases, it can lead to the loss of the hoof if it affects the layers of the skin above the hoof (the coronary band).

The disease is usually evident as soon as foals are born, and small to large patches of skin may be missing from limbs or body, and/or blisters form after mild trauma. Foals may also have oral abnormalities, with premature eruption of teeth, and loss of enamel causing serrated teeth, which in turn leads to gum lesions and bleeding.

2. Intensity of welfare impact

In affected animals, blisters and ulcers on the skin and in the mouth cause considerable pain and distress. Open sores leave the affected foal susceptible to secondary infection, sepsis and consequent malaise. There is no treatment and foals will require euthanasia or will eventually die from secondary infections or complete sloughing of the hooves.

3. Duration of welfare impact

The disease is progressive and within a few days or weeks of birth, foals will die from secondary infection or need to be euthanized by a veterinarian because of the severity of the disease.

4. Number of animals affected

In North America and Canada, the prevalence of carriers for the condition was estimated to be between 17-32% of all Belgian draft horses. These carriers are unaffected themselves but may produce affected offspring if mated with another carrier.

5. Diagnosis

A diagnosis of junctional epidermolysis bullosa may be suspected from the typical clinical signs of skin fragility and blistering associated with the disease. A skin biopsy can identify separation between the epidermal and the dermal layers.

A definitive diagnosis can be made via DNA testing for the mutation responsible for junctional epidermolysis bullosa in draft horses

6. Genetic

Junctional epidermolysis bullosa is an autosomal recessive trait affecting Belgian draft horses. Horses which have two copies of the gene mutation, one from each parent, are homozygous and will develop the condition. Since these horses die shortly after birth, they will never reach sexual maturity and produce their own offspring. Horses which have one copy of the gene mutation, one from one parent, are heterozygous carriers; these horses do not have clinical signs or suffer from the disease and have normal skin. The mating of two heterozygous horses will result in a 25% chance of the offspring being homozygous and affected with junctional epidermolysis bullosa, whilst 50% will be heterozygous carriers for the condition and a further 25% will be clear of the genetic mutation (normal).

The genetic mutation responsible for junctional epidermolysis bullosa disrupts the formation of the protein laminin, which plays an important role in anchoring cells in place and is integral to the structure and function of the dermal-epidermal junction

7. How do you know if an animal is a carrier or likely to become affected?

A genetic test provides the most accurate way to determine whether a Belgian horse can produce affected foals. It can distinguish between horses that are homozygous for the gene (ie that possess two copies of the mutation and are affected by the disease), heterozygous carriers (that are unaffected and possess one copy of the mutated gene), as well as non-affected (no gene mutation) horses

8. Methods and prospects for elimination of the problem

To reduce the prevalence of this recessive inherited disorder, genetic screening for carriers is recommended for all Belgian draft horses that may be used for breeding. The mating of two carriers together should be avoided, since a quarter of the resultant offspring will suffer from the condition and half will be carriers.


For further details about this condition, please click on the following:
(these link to items down this page)


1. Clinical and pathological effects

The skin is the largest organ of the body. It is made up from three layers – the epidermis, the dermis and the subcutaneous layer (see Figure 1).  The epidermis is the protective outer layer of the skin, and is composed of several layers of cells. At the base of the epidermis, there is a thin layer called the basement membrane and this connects the epidermis to the dermis below. This fibrous basement membrane is itself composed of two layers, the outer basal lamina (made up of two sub-layers – the lamina lucida and the lamina densa) and the inner layer of connective tissue which extends from the dermis. The connective tissue attaches to the basal lamina by collagen anchoring fibrils and fibrillin microfibrils.

The dermis provides tensile strength and elasticity to the skin, and it contains blood vessels, skin structures (such as hair follicles and sweat and other glands) and sensory nerve receptors that respond to sensations of touch and temperature. The subcutaneous layer is comprised of fat and muscle tissue that provides insulation and energy (Moriello et al 2011).

Figure 1. A diagram of a section through skin, noting the 3 major layers of epidermis, dermis and subcutis (subcutaneous layer). Image reproduced from Wikivet.net under Public Domain Mark 1.0 (https://en.wikivet.net/File:Skin.png).

Junctional epidermolysis bullosa is a disease of the skin, and belongs to the group of vesiculo-bullous diseases of the epidermis which are all characterised by the formation of a split (vesicle or bulla) between layers of the epidermis, or beneath it at the dermo-epidermal junction or basement membrane.

In horses affected with junctional epidermolysis bullosa, this split is caused by a genetic defect that interferes with the formation of the structural components that allow the layers to adhere to each other. Specifically, there is incomplete synthesis of the structural components of intercellular adhesions (e.g. keratin filaments) and anchoring fibrils (eg collagen). In junctional epidermolysis bullosa, the split forms between the two sub-layers of the basement membrane basal lamina, the lamina lucida and the lamina densa - leaving only the inner lamina densa sub-layer anchored to the underlying dermal collagen (Johnson et al 1988; Figure 2). At this split, when the two sub-layers pull away from each other blisters form. Inflammation at the site of these blisters is usually minimal except where there is secondary infections caused by bacteria (Johnson et al 1988).

Figure 2. A transverse histological skin section showing junctional epidermolysis bullosa. The separation between the dermis (D) and epidermis (E) leads to the formation of a blister (B). The lamina densa is split from the lamina lucida of the basal lamina and remains attached to the dermal collagen. The cornified layer cells (CL) and a hair follicle (HF) are also visible. Image reproduced from (Milenkovic et al 2003) under the Creative Commons Attribution license 4.0. 

Junctional epidermolysis bullosa in Belgian draft horses is a severe form of the disease and is comparable to the severe (Herlitz) form of junctional epidermolysis bullosa in humans (Spirito et al 2002). Splits develop in the skin of the affected animal, and these rapidly progress to erosions and deep ulcerative lesions, especially at pressure points or after mild trauma. Lesions commonly develop over bony prominences of the hock, stifle, hip, elbow, carpus and coronet band of the hoof (Schott & Petersen 2005). In severe cases, it can lead to complete sloughing of the hoof exposing sensitive structures or causing the pedal bone to prolapse through the sole. Sloughing of a hoof occurred in two of six foals with junctional epidermolysis bullosa (Baird et al 2003). These clinical features are shown in Figure 3, below.

The disease is evident as soon as foals are born, and small to large patches of skin may be missing from limbs or body. Irregular, reddened erosions and ulcerations of the skin and mouth develop over pressure points or after mild trauma (Shapiro and McEwen). The skin is fragile and blisters, which can be extensive, commonly develop. Foals may also have a defective enamel matrix of the teeth (enamel hypoplasia), in which the enamel is hard but thin. This causes pitting and irregular serrated edges, leading to lesions and ulceration in the membranes of the mouth. The teeth may also erupt prematurely and central incisors and premolars are present at birth (Schott & Petersen 2005) where in normal horses, they are not usually observed until 8-14 days after birth.

Figure 3. Clinical features of junctional epidermolysis bullosa in affected foals. Extensive absence of the skin on lower limbs and joints is visible (A and B), with ulceration of the gum mucosa (C) and the sloughing of the hoof (D). Images reproduced from (Milenkovic et al 2003) under the Creative Commons Attribution license 4.0.

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2. Intensity of welfare impact

Affected foals may be born with patches of missing skin, particularly on the lower limbs and joints (Spirito et al 2002, Milenkovic et al 2003). The skin is fragile and will break with mild trauma. Blisters and ulcers develop on the skin and in the mouth, and these cause considerable pain and distress. Open sores leave the affected foal susceptible to secondary infection and blood poisoning (septicaemia). Secondary bacterial infection may cause localised swelling, heat and pain. Septicaemia may develop from bacterial infection, leading to fever, nausea and vomiting and severe breathlessness and can be fatal.

Foals will have difficulty nursing due to ulceration in the mouth and may therefore become weakened and thin. In some cases, complete sloughing of the hooves may occur with rupturing of the coronary bands, the soft skin that the hoof grows from. Euthanasia is best option in these cases due to the severity and intractable nature of the problem.

The severity of the disease at birth can vary, but the disease is progressive and there is no curative treatment. Foals will eventually die from secondary infections or complete sloughing of the hooves, which is so severe it requires euthanasia. Once diagnosed, affected foals are commonly euthanased by a veterinarian to prevent prolonged suffering..

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3. Duration of welfare impact

Affected foals may be born with blisters and missing skin, or the blistering and ulceration may develop within the first few days after birth. The disease is progressive and within a few days or weeks of birth, foals will die from secondary infection or will be euthanased by a veterinarian because of the severity of the disease (Spirito et al 2002, Baird et al 2003)

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4. Number of animals affected

In North America, reports of junctional epidermolysis bullosa in Belgian draft foals were first published in late 1980s (Johnson et al 1988, Frame et al 1988), although other reports suggest the condition was observed much earlier (Baird et al 2003).

Between May 2001 and February 2003, 172 Belgian draft horses located on 12 breeding farms in North America were tested for the genetic mutation (LAMC2) responsible for junctional epidermolysis bullosa (Baird et al 2003). Of 172 horses, 57 (32%) were heterozygous carriers for the condition (ie unaffected but able to produce affected offspring if mated with another carrier). Eight of the 12 farms had reported at least one affected foal in the past 5 years.

Of 328 horses registered with the Belgian Draft Horse Corporation of America or Canadian Belgian Horse Association Belgian horses (between October 2002 and May 2003), 56 horses (17%) were heterozygous carriers for the condition (Baird et al 2003).

Heterozygous carriers of the genetic mutation were also identified in the Breton, Comtois, Vlaams Paard, and Belgische Koudbloed Flander draft horse breeds in Europe (Baird et al 2003).

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5. Diagnosis

A diagnosis of junctional epidermolysis bullosa is suspected by typical clinical signs of skin fragility and blistering associated with the disease, and a skin biopsy may be taken to identify separation between the epidermal and the dermal layers (Figure 2).

A definitive diagnosis can be made via DNA testing for the mutation responsible for junctional epidermolysis bullosa in draft horses (Johnson et al 1988).

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6. Genetics

Junctional epidermolysis bullosa is an autosomal recessive trait affecting Belgian horses (Johnson et al 1988, Milenkovic et al 2003). Horses that have two copies of the gene mutation, one from each parent, will be homozygous and be affected with junctional epidermolysis bullosa. Since these horses die shortly after birth, they will never reach sexual maturity and produce offspring. Horses that have one copy of the gene mutation, one from one parent, are heterozygous carriers; these horses do not have clinical signs or suffer from the disease and have normal skin. The mating of two heterozygous horses will result in a 25% chance of the offspring being homozygous affected with junctional epidermolysis bullosa, whilst 50% will be heterozygous carriers for the condition and a further 25% will be clear of the genetic mutation (normal).

The genetic mutation responsible for junctional epidermolysis bullosa disrupts the formation of the protein laminin. Laminin is a heterotrimeric basement membrane protein which is integral to the structure and function of the dermal-epidermal junction, helping to anchor cells in place. It consists of three glycoprotein subunits – α3, β3 and γ2 chains which are encoded by the genes LAMA3, LAMB3 and LAMC2 respectively (Spirito et al 2002). An insertion mutation creates a premature stop codon in the LAMC2 gene, which encodes the laminin γ2 subunit chain (Spirito et al 2002), and this prevents the chain from interacting with the two other subunits, preventing the formation of laminin 5. Laminin 5 is widely distributed in the basement membrane of epithelial tissues and the absence of laminin 5 results in a cleft between the basement membrane zone of the dermal-epidermal junction.

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7. How do you know if an animal is a carrier or likely to become affected?

A genetic test can identify the genetic mutation responsible for junctional epidermolysis bullosa and provides the most accurate way to determine whether a Belgian draft horse can produce affected foals. It can detect horses that are homozygous for the gene (ie possess two copies of the mutation and are affected by the disease), heterozygous carriers (that are unaffected and possess one copy of the mutated gene), as well as non-affected (no gene mutation) horses.

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8. Methods and prospects for elimination of the problem

Horses that are homozygous and affected by this condition are not likely to be bred from, since they die before reaching sexual maturity. To reduce the prevalence of this recessive inherited disorder, genetic screening for carriers is recommended for all Belgian draft horses which may be bred from, especially if there is a history of this condition in siblings, siblings of parents or other relatives. The mating of two carriers together should be avoided, since a quarter of the horses they produce will suffer from the condition and half will be carriers. Only horses without the mutated gene should be used for breeding, or at least carrier horses should not be mated with other carriers. It is also advisable to screen for this genetic mutation in other draft horse breeds, including Breton, Comtois, Vlaams Paard, and Belgische Koudbloed Flander draft horse breeds (Baird et al 2003).

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9. Acknowledgements

UFAW thanks Dr Emma Buckland (BSc PhD), Dr David Brodbelt (MA VetMB PhD DVA DipECVAA MRCVS) and Dr Dan O’Neill (MVB BSc MSc PhD MRCVS) for their work in compiling this section.

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10. References

Baird JD, Millon LV, Dileanis S, Penedo MCT, Charlesworth A, Spirito F and Meneguzzi G (2003) Junctional epidermolysis Bullosa in Belgain draft horses. Proceedings of the American Association of Equine Practioners 49: 122–126

Frame SR, Harrington DD, Fessler J and Frame PF (1988) Hereditary junctional mechanobullous disease in a foal. Journal of the American Veterinary Medical Association 193: 1420–4

Johnson GC, Kohn CW, Johnson CW, Garry F, Scott D and Martin S (1988) Ultrastructure of junctional epidermolysis bullosa in Belgian foals. Journal of Comparative Pathology 99: 329–336

Milenkovic D, Chaffaux S, Taourit S and Guérin G (2003) A mutation in the LAMC2 gene causes the Herlitz junctional epidermolysis bullosa (H-JEB) in two French draft horse breeds. Genetics Selection Evolution 35: 249

Moriello KA, Lloyd JE, Losson BJ, Rosenkrantz W, Talcott PA, Villalobos AE, White PD, Klei TR, Stiller D, White SD and Foil CS (2011) Structure of the Skin in Horses. Merck Veterinary Manual. Merck Sharp & Dohme Corp, USA

Schott HC and Petersen AD (2005) Cutaneous Markers of Disorders Affecting Young Horses. Clinical Techniques in Equine Practice 4: 314–323

Spirito F, Charlesworth A, Linder K, Ortonne J-P, Baird J and Meneguzzi G (2002) Animal models for skin blistering conditions: absence of laminin 5 causes hereditary junctional mechanobullous disease in the Belgian horse. The Journal of Investigative Dermatology 119: 684–91

© UFAW 2016


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